NMB

Summary

NMB (neuromedin B, HGNC:7842) is a protein-coding gene on chromosome 15q25.2, encoding Neuromedin-B (P08949). Stimulates smooth muscle contraction.

This gene encodes a member of the bombesin-like family of neuropeptides, which negatively regulate eating behavior. The encoded protein may regulate colonic smooth muscle contraction through binding to its cognate receptor, the neuromedin B receptor (NMBR). Polymorphisms of this gene may be associated with hunger, weight gain and obesity. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4828 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_021077

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7842
Approved symbol	NMB
Name	neuromedin B
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC2277, MGC3936, MGC17211
Ensembl gene	ENSG00000197696
Ensembl biotype	protein_coding
OMIM	162340
Entrez	4828

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000360476, ENST00000394588

RefSeq mRNA: 2 — MANE Select: NM_021077 NM_021077, NM_205858

CCDS: CCDS10332, CCDS42076

Canonical transcript exons

ENST00000360476 — 3 exons

Exon	Start	End
ENSE00001248612	84657176	84657348
ENSE00001847702	84657996	84658199
ENSE00001918184	84655132	84655409

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 95.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3161 / max 320.7534, expressed in 1415 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151333	7.1879	1391
151334	0.1282	33

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	95.36	silver quality
adipose tissue	UBERON:0001013	92.80	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.66	gold quality
omental fat pad	UBERON:0010414	92.51	gold quality
peritoneum	UBERON:0002358	92.44	gold quality
olfactory bulb	UBERON:0002264	92.10	gold quality
connective tissue	UBERON:0002384	91.75	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.45	gold quality
right adrenal gland	UBERON:0001233	89.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.86	gold quality
left lobe of thyroid gland	UBERON:0001120	88.26	gold quality
left adrenal gland cortex	UBERON:0035825	88.24	gold quality
right lobe of thyroid gland	UBERON:0001119	88.20	gold quality
left adrenal gland	UBERON:0001234	88.20	gold quality
hypothalamus	UBERON:0001898	88.16	gold quality
right adrenal gland cortex	UBERON:0035827	87.59	gold quality
thyroid gland	UBERON:0002046	87.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.13	gold quality
adrenal cortex	UBERON:0001235	86.85	gold quality
tibial nerve	UBERON:0001323	86.36	gold quality
left coronary artery	UBERON:0001626	86.15	gold quality
spinal cord	UBERON:0002240	86.03	gold quality
dorsal root ganglion	UBERON:0000044	85.81	gold quality
adrenal gland	UBERON:0002369	84.80	gold quality
coronary artery	UBERON:0001621	84.77	gold quality
apex of heart	UBERON:0002098	84.33	gold quality
left uterine tube	UBERON:0001303	83.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.41	gold quality
ascending aorta	UBERON:0001496	83.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-95	yes	2147.34
E-ANND-3	yes	7.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting NMB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-6514-5P	95.07	66.02	655

Literature-anchored findings (GeneRIF, showing 10)

• lysosomal degradation of neuromedin B is dependent on tripeptidyl peptidase-I (PMID:15158442)
• NMB and its receptor are coexpressed by proliferating cells in which they act in an autocrine fashion with similar and modest potency in both normal and malignant colonic epithelial cells. (PMID:15528253)
• Associated with eating behaviors (PMID:15585758)
• REsults describe the expression of neuromedin B in adipose tissue and its regulation by changes in energy balance. (PMID:17766645)
• No significant differences in the genotype distribution were demonstrated between normal weight and overweight/obese subjects (PMID:18271693)
• TT genotype of the NMB rs3809508 polymorphism was associated with a higher risk of obesity and moreover, the effects of this polymorphism on anthropometric values were influenced by the maternal educational level. (PMID:20010906)
• There was no association between eating behaviour traits, or anthropometric variables, and NMB p.P73T polymorphism. (PMID:21527296)
• Rs2292462 was associated with left ventricular hypertrophy in type 2 diabetic patients. (PMID:23879873)
• Genetic clues to the mechanism by which MC4R, FTO, and NMB influences changes in BMI and obesity. (PMID:27634552)
• GPNMB is exposed on the surface of dormant breast cancer cells and its activity contributes to the acquisition of stem cell-like properties (PMID:30224376)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nmba	ENSDARG00000068144
danio_rerio	nmbb	ENSDARG00000077167
mus_musculus	Nmb	ENSMUSG00000025723
rattus_norvegicus	Nmb	ENSRNOG00000011011

Paralogs (1): GRP (ENSG00000134443)

Protein

Protein identifiers

Neuromedin-B — P08949 (reviewed: P08949)

All UniProt accessions (1): P08949

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates smooth muscle contraction. Induces sighing by acting directly on the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity. Contributes to the induction of sneezing following exposure to chemical irritants or allergens which causes release of NMB by nasal sensory neurons and activation of NMBR-expressing neurons in the sneeze-evoking region of the brainstem. These in turn activate neurons of the caudal ventral respiratory group, giving rise to the sneezing response. Contributes to induction of acute itch, possibly through activation of the NMBR receptor on dorsal root ganglion neurons. Increases expression of NMBR and steroidogenic mediators STAR, CYP11A1 and HSD3B1 in Leydig cells, induces secretion of testosterone by Leydig cells and also promotes Leydig cell proliferation. Plays a role in the innate immune response to influenza A virus infection by enhancing interferon alpha expression and reducing expression of IL6. Plays a role in CSF1-induced proliferation of osteoclast precursors by contributing to the positive regulation of the expression of the CSF1 receptor CSF1R.

Subcellular location. Secreted. Cell projection. Neuron projection.

Induction. Up-regulated in response to infection with influenza A virus.

Similarity. Belongs to the bombesin/neuromedin-B/ranatensin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P08949-1	1	yes
P08949-2	2

RefSeq proteins (2): NP_066563, NP_995580 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000874	Bombesin	Family

Pfam: PF02044

UniProt features (9 total): peptide 2, signal peptide 1, propeptide 1, modified residue 1, splice variant 1, sequence variant 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8H0P	ELECTRON MICROSCOPY	3.15
1C98	SOLUTION NMR
1C9A	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08949-F1	68.16	0.02

Antibody-complex structures (SAbDab): 1 — 8H0P

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 56

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 194 (showing top): GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, MODULE_16, GOBP_REFLEX, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_6_PRODUCTION

GO Biological Process (19): signal transduction (GO:0007165), positive regulation of cytosolic calcium ion concentration (GO:0007204), neuropeptide signaling pathway (GO:0007218), cell-cell signaling (GO:0007267), negative regulation of interleukin-6 production (GO:0032715), positive regulation of interferon-alpha production (GO:0032727), positive regulation of hormone secretion (GO:0046887), negative regulation of hormone secretion (GO:0046888), arachidonate secretion (GO:0050482), positive regulation of osteoclast proliferation (GO:0090290), antiviral innate immune response (GO:0140374), sneeze reflex (GO:0160023), Leydig cell proliferation (GO:0160024), sensory perception of itch (GO:0160025), positive regulation of respiratory gaseous exchange (GO:1903942), positive regulation of testosterone secretion (GO:2000845), immune system process (GO:0002376), positive regulation of cell population proliferation (GO:0008284), innate immune response (GO:0045087)

GO Molecular Function (4): hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), neuromedin B receptor binding (GO:0031710), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), neuron projection (GO:0043005), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
hormone secretion	2
regulation of hormone secretion	2
cell population proliferation	2
cellular anatomical structure	2
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of biological quality	1
G protein-coupled receptor signaling pathway	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
positive regulation of type I interferon production	1
interferon-alpha production	1
regulation of interferon-alpha production	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of secretion by cell	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of secretion by cell	1
icosanoid secretion	1
arachidonate transport	1
osteoclast proliferation	1
positive regulation of leukocyte proliferation	1
regulation of osteoclast proliferation	1
innate immune response	1
defense response to virus	1
reflex	1
sensory perception	1
respiratory gaseous exchange by respiratory system	1
regulation of respiratory gaseous exchange	1
positive regulation of multicellular organismal process	1
positive regulation of lipid transport	1
testosterone secretion	1
positive regulation of hormone secretion	1
regulation of testosterone secretion	1
biological_process	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NMB	NMBR	P28336	999
NMB	GRP	P07491	987
NMB	GRPR	P30550	897
NMB	BRS3	P32247	896
NMB	TLR4	O00206	744
NMB	NEU1	Q99519	653
NMB	NMS	Q5H8A3	620
NMB	KNG1	P01042	578
NMB	TAC1	P20366	574
NMB	TACR1	P25103	549
NMB	TAC3	Q9UHF0	541
NMB	NPFF	O15130	514
NMB	SST	P01166	509
NMB	TRPC7	Q9HCX4	507
NMB	NTS	P30990	498

IntAct

10 interactions, top by confidence:

A	B	Type	Score
BIRC2	NMB	psi-mi:“MI:0915”(physical association)	0.560
NMB	BIRC2	psi-mi:“MI:0915”(physical association)	0.560
NMB	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
NMB	rep	psi-mi:“MI:0915”(physical association)	0.370
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
PLA2G2D	ZZEF1	psi-mi:“MI:0914”(association)	0.350
NMB	HSPA5	psi-mi:“MI:0914”(association)	0.350
NMB	ALOX12B	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): NMB (Two-hybrid), BIRC2 (Two-hybrid), NMB (Two-hybrid), NMB (Two-hybrid), NMB (Two-hybrid), NMBR (Reconstituted Complex), TXNL4B (Affinity Capture-MS), GID8 (Affinity Capture-MS), NMB (Affinity Capture-MS), ZMYND19 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), MAEA (Affinity Capture-MS), RMND5A (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), HSPA5 (Affinity Capture-MS)

ESM2 similar proteins: D3Z752, M0R8L2, O00230, O15130, O57312, O62827, O77559, O93464, P01143, P01169, P01258, P01297, P08435, P08949, P08989, P10093, P12760, P24393, P35318, P47851, P49188, P53366, P55089, P55090, P55099, P63152, P63153, P81277, P81278, P81615, P81872, P83859, P83860, P83862, Q13519, Q2T9U8, Q6ECK6, Q800I8, Q863C3, Q86UU9

Diamond homologs: P01295, P07492, P08949, P08989, P24393, P29007, P31886, P47851, P63152, P63153, Q863C3, Q8R1I2, P01297, Q2T9U8, Q9CR53

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NMB	up-regulates	NMBR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

34 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

763 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:84657341:G:C	F55L	0.977
15:84657341:G:T	F55L	0.977
15:84657343:A:G	F55L	0.977
15:84658003:C:A	W50C	0.969
15:84658003:C:G	W50C	0.969
15:84657338:C:A	M56I	0.966
15:84657338:C:G	M56I	0.966
15:84657338:C:T	M56I	0.966
15:84657348:C:T	G53D	0.959
15:84657332:C:A	K58N	0.955
15:84657332:C:G	K58N	0.955
15:84657337:C:A	G57C	0.954
15:84657337:C:G	G57R	0.948
15:84657342:A:G	F55S	0.946
15:84657342:A:C	F55C	0.942
15:84657348:C:A	G53V	0.942
15:84657996:C:G	G53R	0.937
15:84657344:G:C	H54Q	0.934
15:84657344:G:T	H54Q	0.934
15:84657996:C:A	G53C	0.933
15:84657336:C:A	G57V	0.931
15:84658005:A:G	W50R	0.931
15:84658005:A:T	W50R	0.931
15:84657336:C:T	G57D	0.922
15:84657346:G:C	H54D	0.906
15:84657998:G:A	T52I	0.892
15:84658013:C:A	G47V	0.886
15:84657329:C:A	K59N	0.881
15:84657329:C:G	K59N	0.881
15:84658001:G:T	A51D	0.879

dbSNP variants (sampled 300 via entrez): RS1000982676 (15:84657627 G>A,T), RS1001374579 (15:84659832 C>A,T), RS1003172401 (15:84659551 T>A), RS1003662221 (15:84658315 G>C,T), RS1003729418 (15:84659721 T>A,G), RS1005530995 (15:84658446 G>C), RS1005719803 (15:84656528 G>A,T), RS1005979595 (15:84658269 A>C,G), RS1006171680 (15:84654665 T>C), RS1007677514 (15:84655658 G>A), RS1007688204 (15:84659015 GAAT>G), RS1007739084 (15:84659197 A>C), RS1010039106 (15:84659908 G>T), RS1010165640 (15:84658546 C>G), RS1010259056 (15:84659516 A>G,T)

Disease associations

OMIM: gene MIM:162340 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Aflatoxin B1	affects expression, increases expression	3
Cisplatin	increases expression, affects cotreatment	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects expression, affects cotreatment	1
dicrotophos	decreases expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
bisphenol S	increases methylation	1
jinfukang	increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Decitabine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Azathioprine	decreases expression	1
Dexamethasone	affects cotreatment, affects expression	1
Doxorubicin	decreases expression	1
Folic Acid	increases expression	1
Gold Sodium Thiomalate	decreases expression	1
Indomethacin	affects cotreatment, affects expression	1
Methotrexate	decreases expression	1
Methylprednisolone	decreases expression	1
Nickel	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.